Safety, Tolerability, and Pharmacokinetics of Oral BI 1358894 in Healthy Japanese Male Volunteers.
Clin Drug Investig
; 44(5): 319-328, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38656736
ABSTRACT
BACKGROUND AND OBJECTIVES:
BI 1358894, a novel small-molecule inhibitor of transient receptor potential canonical ion channels, is under development for treatment of major depressive disorder. Phase I trials assessing the safety and pharmacokinetics of BI 1358894 in Caucasian male healthy volunteers (HVs) have been performed. This Phase I, double-blind, placebo-controlled, parallel-group trial assessed the safety, tolerability and pharmacokinetics of BI 1358894 in Japanese male HVs.METHODS:
Male HVs were randomized to receive oral BI 1358894 (n = 18) or placebo (n = 6) after a high-fat, high-calorie meal within three dose groups (50 mg, 100 mg, 200 mg), administered sequentially in dose-ascending order. The primary endpoint was number of HVs with drug-related adverse events (DRAEs). Secondary endpoints were the pharmacokinetic parameters of BI 1358894.RESULTS:
Overall, 24 male HVs entered the trial [mean (standard deviation) age 30.0 (7.6) years]. DRAEs occurred in 3/18 HVs (BI 1358894 100 mg group one HV experienced dizziness and headache; BI 1358894 200 mg group one HV experienced headache, another reported sleep disorder). BI 1358894 exposure increased dose dependently and proportionally, peaking 4-6 h after administration before declining in a multiphasic manner with a terminal elimination half-life of ~70 h in the 50 mg and 100 mg dose groups, and 203 h in the 200 mg dose group.CONCLUSION:
BI 1358894 was well tolerated with a favorable pharmacokinetic profile in Japanese male HVs, similar to findings from a previous study in Caucasian male HVs. TRIAL REGISTRATION ClinicalTrials.gov (NCT03875001; 08-Mar-2019).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Orgânicos
/
Voluntários Saudáveis
Limite:
Adult
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Humans
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Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
Clin Drug Investig
Ano de publicação:
2024
Tipo de documento:
Article